Immune to addiction: the ethical dimensions of vaccines against substance abuse.

Promising advances have been made in recent years for a unique class of immunotherapies that use vaccination to combat substance-use disorders. Although such vaccines are potentially useful for addictions, they raise a variety of ethical and social questions.

Research involving the recently deceased: ethics questions that must be answered.

Research involving recently deceased humans that are physiologically maintained following declaration of death by neurologic criteria-or 'research involving the recently deceased'-can fill a translational research gap while reducing harm to animals and living human subjects. It also creates new challenges for honouring the donor's legacy, respecting the rights of donor loved ones, resource allocation and public health. As this research model gains traction, new empirical ethics questions must be answered to preserve public trust in all forms of tissue donation and in the practice of medicine while respecting the legacy of the deceased and the rights of donor loved ones. This article suggests several topics for immediate investigation to understand the attitudes and experiences of researchers, clinical collaborators, donor loved ones and the public to ensure research involving the recently deceased advances ethically.

Consideration and Disclosure of Group Risks in Genomics and Other Data-Centric Research: Does the Common Rule Need Revision?

Harms and risks to groups and third-parties can be significant in the context of research, particularly in data-centric studies involving genomic, artificial intelligence, and/or machine learning technologies. This article explores whether and how United States federal regulations should be adapted to better align with current ethical thinking and protect group interests. Three aspects of the Common Rule deserve attention and reconsideration with respect to group interests: institutional review board (IRB) assessment of the risks/benefits of research; disclosure requirements in the informed consent process; and criteria for waivers of informed consent. In accordance with respect for persons and communities, investigators and IRBs should systematically consider potential group harm when designing and reviewing protocols, respectively. Research participants should be informed about any potential group harm in the consent process. We call for additional public discussion, empirical research, and normative analysis on these issues to determine the right regulatory and policy path forward.

Response to American College of Physician's statement on the ethics of transplant after normothermic regional perfusion.

This paper responds to the position statement released by the American College of Physicians (ACP) entitled "Ethics, Determination of Death, and Organ Transplantation in Normothermic Regional Perfusion (NRP) with Controlled Donation after Circulatory Determination of Death (cDCD): American College of Physicians Statement of Concern." The ACP's statement engages with critical ethical issues surrounding cDCD NRP, but several of their conclusions are flawed. Contrary to the statement, the practice respects the dead donor rule and the legal definition of death while honoring the wishes of the deceased and their loved ones to help save the lives of those in need of organ transplants. cDCD NRP is well established in many countries, it can enhance trust in medical practice and organ donation, and will increase the availability of optimal organs for life-saving transplants.

Emerging technologies and ethics-exogenic chimeric humanized organs.

Organ transplantation is limited due to the scarcity of donor organs. In order to expand the supply of organs for transplantation, interspecies chimeras have been examined as a potential future source of humanized organs. Recent studies using gene editing technologies in combination with somatic cell nuclear transfer technology and hiPSCs successfully engineered humanized skeletal muscle in the porcine embryo. As these technologies progress, there are ethical issues that warrant consideration and dialogue.

Promoting COVID-19 vaccine acceptance: recommendations from the Lancet Commission on Vaccine Refusal, Acceptance, and Demand in the USA.

Since the first case of COVID-19 was identified in the USA in January, 2020, over 46 million people in the country have tested positive for SARS-CoV-2 infection. Several COVID-19 vaccines have received emergency use authorisations from the US Food and Drug Administration, with the Pfizer-BioNTech vaccine receiving full approval on Aug 23, 2021. When paired with masking, physical distancing, and ventilation, COVID-19 vaccines are the best intervention to sustainably control the pandemic. However, surveys have consistently found that a sizeable minority of US residents do not plan to get a COVID-19 vaccine. The most severe consequence of an inadequate uptake of COVID-19 vaccines has been sustained community transmission (including of the delta [B.1.617.2] variant, a surge of which began in July, 2021). Exacerbating the direct impact of the virus, a low uptake of COVID-19 vaccines will prolong the social and economic repercussions of the pandemic on families and communities, especially low-income and minority ethnic groups, into 2022, or even longer. The scale and challenges of the COVID-19 vaccination campaign are unprecedented. Therefore, through a series of recommendations, we present a coordinated, evidence-based education, communication, and behavioural intervention strategy that is likely to improve the success of COVID-19 vaccine programmes across the USA.

Getting serious about the challenge of regulating germline gene therapy.

The announcement of He Jiankui's germline editing of human embryos has been followed by a torrent of almost universal criticism of the claim on scientific and ethical grounds. That criticism is warranted. There is little room for anything other than vociferous condemnation of He's announcement. Presenting the results of groundbreaking work by press conference and YouTube is not science. The issue now is not whether the work supporting the claims reported from China was done in an ethical manner. It was not. What is required to move forward is a justification for doing germline editing in humans. Many think there is none, and prohibitions abound. If such work is justifiable, a serious, rigorous framework must be imposed that insures that such research is done following the highest ethical standards that both protect human subjects and insure public trust and support.

Priority vaccination for mental illness, developmental or intellectual disability.

Coronavirus vaccines have made their debut. Now, allocation practices have stepped into the spotlight. Following Centers for Disease Control and Prevention guidelines, states and healthcare institutions initially prioritised healthcare personnel and elderly residents of congregant facilities; other groups at elevated risk for severe complications are now becoming eligible through locally administered programmes. The question remains, however: who else should be prioritised for immunisation? Here, we call attention to individuals institutionalised with severe mental illnesses and/or developmental or intellectual disabilities-a group highly susceptible to the damages of COVID-19, recent research shows, and critical to consider for priority vaccination. The language describing both federal-level and state-level intentions for this population remains largely vague, despite the population's diversity across age, diagnosis, functional status and living arrangement. Such absence of specificity, in turn, leaves room for confusion and even neglect of various subgroups. We review data stressing this group's vulnerability, as well as select state plans for priority vaccination, highlighting the importance of clarity when describing intentions to vaccinate, or even generally care for, diverse populations composed of distinct subgroups in need.

Virtual surgical planning and data ownership: Navigating the provider-patient-vendor relationship.

The practice of modern craniomaxillofacial surgery has been defined by emergent technologies allowing for the acquisition, storage, utilization, and transfer of massive amounts of sensitive and identifiable patient data. This alone has thrust providers into an unlikely and unprecedented role as the stewards of vast databases of digital information. This data powers the potent surgical tool of virtual surgical planning, a method by which craniomaxillofacial surgeons plan and simulate procedural outcomes in a digital environment. Further complicating this new terrain is the involvement of third-party contractors-a necessary presence in bringing raw data to bear in the office, virtual space, and operating room. The individual privileges and responsibilities of patients, providers, and vendors towards data are situated within the most recent U.S. court rulings and regulations. This paper offers guidance for overseeing the safe and responsible transfer to third-party contractors, and provides suggestions for negotiating the trinary relationship between physicians, their patients, and the vendors offering this transformative technology.

The changing world of IVF: the pros and cons of new business models offering assisted reproductive technologies.

This analysis contrasts traditional not-for-profit academic with new corporate practices of reproductive medicine and offers an assessment of risks to quality of patient care with investors entering the for-profit reproductive medicine market. Large corporate enterprises may have a global impact on access to care while at the same time is putting at risk the training of the next generation of reproductive medicine specialists.

Revisiting selected ethical aspects of current clinical in vitro fertilization (IVF) practice.

Ethical considerations are central to all medicine though, likely, nowhere more essential than in the practice of reproductive endocrinology and infertility. Through in vitro fertilization (IVF), this is the only field in medicine involved in creating human life. IVF has, indeed, so far led to close to 10 million births worldwide. Yet, relating to substantial changes in clinical practice of IVF, the medical literature has remained surprisingly quiet over the last two decades. Major changes especially since 2010, however, call for an updated commentary. Three key changes deserve special notice: Starting out as a strictly medical service, IVF in recent years, in efforts to expand female reproductive lifespans in a process given the term "planned" oocyte cryopreservation, increasingly became more socially motivated. The IVF field also increasingly underwent industrialization and commoditization by outside financial interests. Finally, at least partially driven by industrialization and commoditization, so-called add-ons, the term describing mostly unvalidated tests and procedures added to IVF since 2010, have been held responsible for worldwide declines in fresh, non-donor live birthrates after IVF, to levels not seen since the mid-1990s. We here, therefore, do not offer a review of bioethical considerations regarding IVF as a fertility treatment, but attempt to point out ethical issues that arose because of major recent changes in clinical IVF practice.

Should Compensation for Organ Donation Be Allowed?

The need for organs to transplant is clear. Due to the lack of transplants, people suffer, they die, and the cost of taking care of them until they die is huge. There is general agreement that it would be good to increase the supply of organs in order to meet the demand for organ transplantation.

Combined Analysis of Asthma Safety Trials of Long-Acting ß2-Agonists.

BACKGROUND: Safety concerns regarding long-acting ß2-agonists (LABAs) in asthma management were initially identified in a large postmarketing trial in which the risk of death was increased. In 2010, the Food and Drug Administration (FDA) mandated that the four companies marketing LABAs for asthma perform prospective, randomized, controlled trials comparing the safety of combination therapy with a LABA plus an inhaled glucocorticoid with that of an inhaled glucocorticoid alone in adolescents (12 to 17 years of age) and adults. In conjunction with the FDA, the manufacturers harmonized their trial methods to allow an independent joint oversight committee to provide a final combined analysis of the four trials. METHODS: As members of the joint oversight committee, we performed a combined analysis of the four trials comparing an inhaled glucocorticoid plus a LABA (combination therapy) with an inhaled glucocorticoid alone. The primary outcome was a composite of asthma-related intubation or death. Post hoc secondary outcomes included serious asthma-related events and asthma exacerbations. RESULTS: Among the 36,010 patients in the intention-to-treat study, there were three asthma-related intubations (two in the inhaled-glucocorticoid group and one in the combination-therapy group) and two asthma-related deaths (both in the combination-therapy group) in 4 patients. In the secondary analysis of serious asthma-related events (a composite of hospitalization, intubation, or death), 108 of 18,006 patients (0.60%) in the inhaled-glucocorticoid group and 119 of 18,004 patients (0.66%) in the combination-therapy group had at least one composite event (relative risk in the combination-therapy group, 1.09; 95% confidence interval [CI], 0.83 to 1.43; P=0.55); 2100 patients in the inhaled-glucocorticoid group (11.7%) and 1768 in the combination-therapy group (9.8%) had at least one asthma exacerbation (relative risk, 0.83; 95% CI, 0.78 to 0.89; P<0.001). CONCLUSIONS: Combination therapy with a LABA plus an inhaled glucocorticoid did not result in a significantly higher risk of serious asthma-related events than treatment with an inhaled glucocorticoid alone but resulted in significantly fewer asthma exacerbations.

Science in the fight to uphold the rights of children.

The United States is the only major nation to not yet have ratified the United Nations Convention on the Rights of the Child (UNCRC). Recently, there has been an erosion of the rights of children across America, Europe, and elsewhere, but through science, we may have an opportunity to counter some of this alarming trend. In the area of vaccines, the scientific community can raise its voice on the dangers that nonmedical exemptions and delays pose to children at risk for measles, influenza, and other childhood illnesses. Poverty places infants and children at high risk for illness and homelessness. Gun violence and gun-related accidents are killing on average four American children daily, and climate change is promoting global pediatric malnutrition. Increasing international, federal, and state support to seek innovative solutions to these and related issues is a moral imperative.

Ethical considerations regarding COVID-19 vaccination for transplant candidates and recipients.

Solid organ transplant (SOT) candidates and recipients were not included in the COVID-19 vaccine trials that have justified vaccine administration to millions worldwide and will be critical to ending the pandemic. The risks of COVID-19 for SOT candidates and recipients combined with data about this population's response to other vaccines has led to transplant centers recommending vaccination for their candidates and recipients in accordance with guidance from major transplant organizations. Relevant ethics considerations include: weighing the low risk of vaccination causing transplant complications against potentially limited antibody response of vaccines for transplant recipients; the equitable distribution of vaccines among vulnerable populations; the duty to steward and respect organs as limited resources; the duty to support vaccination; and patient autonomy. Vaccinated transplant patients and candidates should also consider participating in research studies to better understand the efficacy and potential long-term risks in this patient population. There are difficult scenarios, like timing transplant after second vaccine dose, when to administer the second dose to a partially vaccinated candidate who gets an organ match, whether to vaccinate a recent transplant recipient with low exposure risk and which vaccine to use. Here we provide ethics considerations for vaccinating different groups within the transplant population.

Helpful Lessons and Cautionary Tales: How Should COVID-19 Drug Development and Access Inform Approaches to Non-Pandemic Diseases?

After witnessing extraordinary scientific and regulatory efforts to speed development of and access to new COVID-19 interventions, patients facing other serious diseases have begun to ask "where's our Operation Warp Speed?" and "why isn't Emergency Use Authorization an option for our health crises?" Although this pandemic bears a number of unique features, the response to COVID-19 offers translatable lessons, in both its successes and failures, for non-pandemic diseases. These include the importance of collaborating across sectors, supporting the highest-priority research efforts, adopting rigorous and innovative trial designs, and sharing reliable information quickly. In addition, the regulatory response to the pandemic demonstrates that lowering standards for marketing authorization can result in increased safety concerns, missed opportunities for research and treatment, and delays in determining what works. Accordingly, policymakers and patient advocates seeking to build on the COVID-19 experience for non-pandemic diseases with unmet treatment needs should focus their efforts on promoting robust and efficient research designs, improving access to clinical trials, and facilitating use of the Food and Drug Administration's existing Expanded Access pathway.

Knowledge and Attitudes Toward Covid-19 and Vaccines Among a New York Haredi-Orthodox Jewish Community.

The Covid-19 pandemic has exposed the difficulty of the US public health system to respond effectively to vulnerable subpopulations, causing disproportionate rates of morbidity and mortality. New York Haredi-Orthodox Jewish communities represent a group that have been heavily impacted by Covid-19. Little research has examined their experience or perceptions toward Covid-19 and vaccines. We conducted a cross-sectional, observational study to explore the experience of Covid-19 among Haredim. Paper surveys were self-administered between December 2020 and January 2021 in Haredi neighborhood pediatricians' offices in Brooklyn, New York. Of 102 respondents, 43% reported either a positive SARS-CoV-2 viral or antibody test. Participants trusted their physicians, Orthodox medical organizations, and rabbinic leaders for medical information. Knowledge of Covid-19 transmission and risk was good (69% answered ≥ 4/6 questions correctly). Only 12% of respondents would accept a Covid-19 vaccine, 41% were undecided and 47% were strongly hesitant. Independent predictors of strong vaccine hesitancy included believing natural infection to be better than vaccination for developing immunity (adjusted odds ratio [aOR] 4.28; 95% confidence interval [CI] 1.23-14.86), agreement that prior infection provides a path toward resuming communal life (aOR 4.10; 95% CI 1.22-13.77), and pandemic-related loss of trust in physicians (aOR 5.01; 95% CI 1.05-23.96). The primary disseminators of health information for self-protective religious communities should be stakeholders who understand these groups' unique health needs. In communities with significant Covid-19 experience, vaccination messaging may need to be tailored toward protecting infection-naïve individuals and boosting natural immunity against emerging variants.

Ventilator Triage Policies During the COVID-19 Pandemic at U.S. Hospitals Associated With Members of the Association of Bioethics Program Directors.

BACKGROUND: The coronavirus disease 2019 pandemic has or threatens to overwhelm health care systems. Many institutions are developing ventilator triage policies. OBJECTIVE: To characterize the development of ventilator triage policies and compare policy content. DESIGN: Survey and mixed-methods content analysis. SETTING: North American hospitals associated with members of the Association of Bioethics Program Directors. PARTICIPANTS: Program directors. MEASUREMENTS: Characteristics of institutions and policies, including triage criteria and triage committee membership. RESULTS: Sixty-seven program directors responded (response rate, 91.8%); 36 (53.7%) hospitals did not yet have a policy, and 7 (10.4%) hospitals' policies could not be shared. The 29 institutions providing policies were relatively evenly distributed among the 4 U.S. geographic regions (range, 5 to 9 policies per region). Among the 26 unique policies analyzed, 3 (11.3%) were produced by state health departments. The most frequently cited triage criteria were benefit (25 policies [96.2%]), need (14 [53.8%]), age (13 [50.0%]), conservation of resources (10 [38.5%]), and lottery (9 [34.6%]). Twenty-one (80.8%) policies use scoring systems, and 20 of these (95.2%) use a version of the Sequential Organ Failure Assessment score. Among the policies that specify the triage team's composition (23 [88.5%]), all require or recommend a physician member, 20 (87.0%) a nurse, 16 (69.6%) an ethicist, 8 (34.8%) a chaplain, and 8 (34.8%) a respiratory therapist. Thirteen (50.0% of all policies) require or recommend that those making triage decisions not be involved in direct patient care, but only 2 (7.7%) require that their decisions be blinded to ethically irrelevant considerations. LIMITATION: The results may not be generalizable to institutions without academic bioethics programs. CONCLUSION: Over one half of respondents did not have ventilator triage policies. Policies have substantial heterogeneity, and many omit guidance on fair implementation. PRIMARY FUNDING SOURCE: None.

Importance of Pediatric Inclusion in COVID-19 Therapeutic Trials.

Pediatric patients are excluded from most coronavirus disease 2019 (COVID-19) therapeutic trials. We outline a rationale for the inclusion of children in COVID-19 therapeutic trials, which enabled us to include children of all ages in a therapeutic COVID-19 trial at our institution.

The unique moral permissibility of uncontrolled lung donation after circulatory death.

Implementing uncontrolled donation after circulatory determination of death (uDCDD) in the United States could markedly improve supply of donor lungs for patients in need of transplants. Evidence from US pilot programs suggests families support uDCDD, but only if they are asked permission for using invasive organ preservation procedures prior to initiation. However, non-invasive strategies that confine oxygenation to lungs may be applicable to the overwhelming majority of potential uDCDD donors that have airway devices in place as part of standard resuscitation. We propose an ethical framework for lung uDCDD by: (a) initiating post mortem preservation without requiring prior permission to protect the opportunity for donation until an authorized party can be found; (b) using non-invasive strategies that confine oxygenation to lungs; and (c) maintaining strict separation between the healthcare team and the organ preservation team. Attempting uDCDD in this way has great potential to obtain more transplantable lungs while respecting donor autonomy and family wishes, securing public support, and enabling authorized persons to affirm or cease preservation decisions without requiring evidence of prior organ donation intent. It ensures prioritization of life-saving, the opportunity to allow willing donors to donate, and respect for bodily integrity while adhering to current ethical norms.